RESUMO
Although sequence variants in CD2-associated protein (CD2AP) have been identified in patients with focal segmental glomerulosclerosis (FSGS), definitive proof of causality in human disease is meager. By whole-exome sequencing, we identified a homozygous frame-shift mutation in CD2AP (p.S198fs) in three siblings born of consanguineous parents who developed childhood-onset FSGS and end stage renal disease. When the same frameshift mutation was introduced in mice by gene editing, the mice developed FSGS and kidney failure. These results provide conclusive evidence that homozygous mutation of CD2AP causes FSGS in humans.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas do Citoesqueleto/genética , Glomerulosclerose Segmentar e Focal/genética , Falência Renal Crônica/patologia , Animais , Consanguinidade , Modelos Animais de Doenças , Progressão da Doença , Feminino , Mutação da Fase de Leitura , Edição de Genes , Técnicas de Introdução de Genes , Glomerulosclerose Segmentar e Focal/patologia , Homozigoto , Humanos , Falência Renal Crônica/genética , Masculino , Camundongos , Camundongos Transgênicos , Linhagem , Sequenciamento do ExomaRESUMO
BACKGROUND: Postinfectious glomerulonephritis due to parvovirus B19 during pregnancy is not described in the literature. OBJECTIVE: A case and renal biopsy of postinfectious glomerulonephritis due to parvovirus B19 during pregnancy is presented. DISCUSSION AND CONCLUSIONS: The patient contracted "fifth disease," parvovirus B19, in the 10th week of pregnancy, and 2 weeks later developed hypertension, nephrotic range proteinuria, pleural effusions, and evidence of pure red cell aplasia. Serum parvovirus B19 IgM was positive; a renal biopsy was performed, revealing diffuse proliferative glomerulonephritis with immunofluorescent and electron microscopic changes consistent with postinfectious glomerulonephritis. Renal, hemodynamical, and hematological parameters returned to normal by the 16th week gestation, and the pregnancy proceeded without further complication to the mother, with term delivery of a healthy infant.